The proposed research is a methodical investigation into the mechanisms by which morphine, heroin, beta-endorphin and other synthetic and endogenous opioid substances alter central and peripheral neural mechanisms which control intestinal motility. The anatomical and neurochemical mechanisms responsible for acute and chronic constipation and opioid withdrawal diarrhea will be investigated. Present evidence suggests that opioid substances act in the brain to alter neural outflow to the intestinal motility. Opioid substances increase contractions of intestinal smooth muscle and increase resistance to flow, thus producing failure of transit and constipation. Release of intestinal 5-hydroxytrytamine (5-HT) is a crucial event in the intestinal stimulatory effects of morphine and related drugs. The 5-HT activates intramural cholinergic neurons which release acetycholine, thus initiating intestinal contractions. Other neurotransmitter mediators will be identified in the proposed research. Opioid substances act on multiple types of intestinal opioid receptors to stimulate or inhibit intestinal contractions. Different types of intestinal opioid receptors may be linked to distinct neurotransmitter pathways, one involving 5-HT and acetycholine. Other pathways may utilize substance P, adenosine triphosphate, neurotensin, or vasoactive intestinal peptide.